L-Lactate Promotes Adult Hippocampal Neurogenesis

Abstract

Neurogenesis, the formation of new neurons in the adult brain, is important for memory formation and extinction. One of the most studied external interventions that affect the rate of adult neurogenesis is physical exercise. Physical exercise promotes adult neurogenesis via several factors including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Here, we identified L -lactate, a physical exercise-induced metabolite, as a factor that promotes adult hippocampal neurogenesis. While prolonged exposure to L -lactate promoted neurogenesis, no beneficial effect was exerted on cognitive learning and memory. Systemic pharmacological blocking of monocarboxylate transporter 2 (MCT2), which transports L -lactate to the brain, prevented lactate-induced neurogenesis, while 3,5-dihydroxybenzoic acid (3,5-DHBA), an agonist for the lactate-receptor hydroxycarboxylic acid receptor 1 (HCAR1), did not affect adult neurogenesis. These data suggest that L -lactate partially mediates the effect of physical exercise on adult neurogenesis, but not cognition, in a MCT2-dependent manner.

<p>Effect of Multicomponent Exercise and Nutrition Support on the Cognitive Function of Older Adults: A Randomized Controlled Trial</p>

“…It has been demonstrated that physical exercise increases BDNF levels 45. Thus, the synergistic effect of soy and exercise shown in our study might be due to increased BDNF levels that promote several aspects of brain function.…”

Exogenous L-lactate promotes astrocyte plasticity but is not sufficient for enhancing striatal synaptogenesis or motor behavior in mice

“…We observed that the peripheral administration of L-lactate did not lead to changes in either synaptogenesis, as defined as changes in PSD-95 or synaptophysin, within the STR, nor improve motor behavior. This in contrast to reports demonstrating that the administration of L-lactate to the hippocampus promotes both neurogenesis and improved cognitive behavior (Lev-Vachnish et al, 2019;Rice et al, 2002).…”

Sensing the Environment: Extracellular Lactate Levels Control Adult Neurogenesis

“…The data shown in this study further support that microenvironmental changes in lactate can have a direct effect on NSC proliferation. Another recent publication observed increased numbers of newborn neurons with lactate injections, without effects on proliferation or early differentiation and without alteration in cognition (Lev-Vachnish et al, 2019). The dosing and exposure to lactate were different in these two studies.…”